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White Matter Diseases



White Matter Disease Research Faculty
Mark Brown, PhD
David Miller, PhD

In MRI scans, MS patients show focal areas of demylination (lesions) in the white matter of the brain.  Previous studies have shown that the MTR in the normal appearing white matter (NAWM) in MS patients shows subtle differences from NAWM in healthy controls, indicating abnormality even in areas not displaying obvious injury.  We are working with subjects in the earliest stages of MS to try to determine how soon these subtler effects show up, in the hopes that it will provide new clues about the early course of the illness.  With DTI, we are looking at metrics such as the fractional anisotropy (FA), which can indicate changes in the axonal fiber bundles on the cellular level.  DTI data is also used for tractography, which creates pictures of the axonal fiber bundles from the DTI data. The goal is to develop a process to identify and then interrogate neuronal fibers that are anatomically related to focal demyelinating lesions.  The strategy is to study cases of early MS, identify fibers transiting the focal lesion and reaching a  distant structure (corpus callosum), and then interrogate fibers (in corpus callosum) by MRI methods (MTR, FA) distant from focal lesion.  Ultimately we would like to detect and measure neuronal fiber injury/degeneration in vivo.  We are particularly interested in the corpus callosum due to its role as the connection between the two hemispheres of the brain.  A mystery in MS is why the corpus callosum suffers as relatively high amount of injury (as evidenced by shrinking and thinning), yet has relatively few focal lesions. 

We start with the anatomic images and segment out the focal lesions. We then create the full complicated model including streamtubes in red  and streamsurfaces in green.  We then cull the tractography axonal bundles to include only bundles intersecting lesions, and then finally only bundles which intersect both lesions and the corpus callosum. 


Figure above shows the results in a case of early MS. The images show few T2 lesions, and if you could see these it is obvious their connectivity to callosum or other tracts would be indeterminate. On the bottom the progression to the model culled to lesion and corpus callosum.  As can be seen many axonal bundles connect the callosum to T2 lesions, even though there are few lesions in the callosum itself.